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Use of genome-wide SNP homozygosity mapping in small pedigrees to identify new mutations in VSX2 causing recessive microphthalmia and a semidominant inner retinal dystrophy

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Mutations in the visual system homeobox 2 gene (VSX2, also known as CHX10), which encodes a retinal transcription factor from the paired homeobox family, have been implicated in recessive isolated microphthalmia. In this study, we use genome-wide single nucleotide polymorphism homozygosity mapping in unrelated small consanguineous pedigrees and a candidate gene approach to identify three further causative VSX2 mutations (two novel and one previously reported). All affected individuals with homozygous mutations had bilateral anophthalmia or severe microphthalmia with absent vision. In addition, we identified a novel inner retinal dystrophy in two carrier parents suggesting a semidominant effect for this particular VSX2 mutation. A further study of individuals with retinal degenerative conditions may reveal a causative role for heterozygous mutations in VSX2.

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We thank the affected individuals and their families for their enthusiastic participation in this study. We are grateful to Dr Angela Martin for research co-ordination and all the referring clinicians, in particular Mr Nick George, Mr Richard Markham and Dr Rania El Essawy. N.R. is a Senior Surgical Scientist supported by the Academy of Medical Sciences/The Health Foundation. We gratefully acknowledge the generous support by grants from Newlife (SUI), VICTA (Visually Impaired Children Taking Action), late Henri Ernest Polak Trust (AW), MACS (Microphthalmia, Anophthalmia Children’s Society) and the National Institute for Health Research UK (Moorfields Eye Hospital Biomedical Research Centre; GEH).

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Correspondence to Nicola K. Ragge.

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Iseri, S.U., Wyatt, A.W., Nürnberg, G. et al. Use of genome-wide SNP homozygosity mapping in small pedigrees to identify new mutations in VSX2 causing recessive microphthalmia and a semidominant inner retinal dystrophy. Hum Genet 128, 51–60 (2010). https://doi.org/10.1007/s00439-010-0823-6

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  • Bipolar Cell
  • Visually Evoke Potential
  • High Resolution Melting
  • Consanguineous Parent
  • Retinal Dystrophy